M2M Exam 1 Diseases

Question 1

Lesch-Nyhan syndrome

Answer 1

This is an X-linked recessive disease.

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme.

Defect in the HPRT1 gene, needed for the synthesis of HGPRT

This enzyme is usually involved in salvaging the purines hypoxanthine and guanine.

Clinical findings:

• Retardation
• Hyperuricemia (excess of uric acid in the blood).
• SELF-MUTILATION

Question 2

How do drugs such as DDI (dideoxyinosine) and nucleoside drugs like AZT (Azidothymine) inhibit DNA synthesis in HIV by reverse transcriptase?

Answer 2

These act as nucleoside analogs due to their similar chemical structure to nucleosides, but they lack the 3’-OH group. This terminated polimerization by reverse transcriptase.

Question 3

Bloom Syndrome

Answer 3

This is an autosomal recessive disorder related to defects in the DNA repair machinery.

It is related to mutation of RecQ helicase: BLM in this case.

Characterized by premature aging, increases cancer risk and cardiovascular problems.

There is an increased risk for developing gastrointestinal tumors and malignant lymphoma.

Question 4

Hereditary nonpolyposis colon cancer (HNPCC; Lynch Syndrome)

Answer 4

This makes a person be in increased risk of colorectal cancers without previous polyps.

It is cuased by a germline mutation that inactivates DNA MISMATCH (MMR) repair genes, which causes a microsatellite repeat replication error (called microsatellite instability).

Question 5

Hemophilia B Leyden

Answer 5

X-linked recessive disorder that affects clotting.

Affected males have less than 1% of normal factor IX active until puberty due to inherited mutations in a DNA control element in the promoter region of Factor IX gene, which prevents the binding of appropiate transcription activators.

How does it change at puberty?

At puberty, alterntive transcription activators can bind overlapping sites in the promoter, since at puberty the androgen receptor becomes active. Thus, males after puberty can make up to 60% the normal amount of factor IX.

Question 6

Fragile X Syndrome

Answer 6

This is a X-linked recessive disorder

Clinical presentations:

-Mental retardation

-Dysmorphic facial features (long face, large mandible, everted ears).

-Postpubertal macroorchidism (enlarged testis)

Where is the CGG repeat most concentrated on?

In the *5’ region of the FMR1 gene facilitates methylation of the cytosine residues in CpG islands and transcriptional inactivation of the FMR1 gene.

What is a normal amount of repeats?

Normal males have 6-50 or so CGG repeats in this region, however, affected males have an expansion of this repeat sequence (>200 copies)- leading to increased transcriptional silencing of the FMR1 gene.